Biodegradable Polymer Versus Polymer-Free Ultrathin Sirolimus-Eluting Stents: Analysis of the Stent Arm Registry From the HOST-IDEA Randomized Trial.

BACKGROUND: The efficacy and safety of each third-generation drug-eluting stent with ultrathin struts and advanced polymer technology remain unclear. We investigated the clinical outcomes of percutaneous coronary intervention using the Coroflex ISAR polymer-free sirolimus-eluting stent (SES) or Orsiro biodegradable polymer SES. METHODS: The HOST-IDEA trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Coronary Intervention With Next-Generation Drug-Eluting Stent Platforms and Abbreviated Dual Antiplatelet Therapy), initially designed with a 2×2 factorial approach, sought to randomize patients undergoing percutaneous coronary intervention based on dual antiplatelet therapy duration (3 versus 12 months) and stent type (Coroflex ISAR versus Orsiro). Despite randomizing 2013 patients for dual antiplatelet therapy duration, the stent arm transitioned to a registry format during the trial. Among these, 328 individuals (16.3%) were randomized for Coroflex ISAR or Orsiro SES, while 1685 (83.7%) underwent percutaneous coronary intervention without stent-type randomization. In this study, the Coroflex ISAR (n=559) and Orsiro groups (n=1449) were matched using a propensity score. The prespecified primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization at 12 months. RESULTS: The baseline patient and procedural characteristics were well balanced between the Coroflex ISAR and Orsiro groups after propensity score matching (n=559, each group). The Coroflex ISAR group was significantly associated with a higher rate of target lesion failure, mainly driven by clinically driven target lesion revascularization, compared with the Orsiro group (3.4% versus 1.1%; hazard ratio, 3.21 [95% CI, 1.28-8.05]; P=0.01). A higher risk of target lesion failure in the Coroflex ISAR group was consistently observed across various subgroups. The rates of any bleeding (hazard ratio, 0.85 [95% CI, 0.51-1.40]; P=0.52) and major bleeding (hazard ratio, 1.58 [95% CI, 0.61-4.08]; P=0.34) were comparable between the 2 groups. CONCLUSIONS: In this propensity score-matched analysis of the stent arm registry from the HOST-IDEA trial, the Orsiro SES was associated with significantly better outcomes in terms of 1-year target lesion failure, mainly driven by clinically driven target lesion revascularization, than the Coroflex ISAR SES. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02601157.

Serum and urine lipidomic profiles identify biomarkers diagnostic for seropositive and seronegative rheumatoid arthritis.

Objective: Seronegative rheumatoid arthritis (RA) is defined as RA without circulating autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies; thus, early diagnosis of seronegative RA can be challenging. Here, we aimed to identify diagnostic biomarkers for seronegative RA by performing lipidomic analyses of sera and urine samples from patients with RA. Methods: We performed untargeted lipidomic analysis of sera and urine samples from 111 RA patients, 45 osteoarthritis (OA) patients, and 25 healthy controls (HC). These samples were divided into a discovery cohort (n = 97) and a validation cohort (n = 84). Serum samples from 20 patients with systemic lupus erythematosus (SLE) were also used for validation. Results: The serum lipidome profile of RA was distinguishable from that of OA and HC. We identified a panel of ten serum lipids and three urine lipids in the discovery cohort that showed the most significant differences. These were deemed potential lipid biomarker candidates for RA. The serum lipid panel was tested using a validation cohort; the results revealed an accuracy of 79%, a sensitivity of 71%, and a specificity of 86%. Both seropositive and seronegative RA patients were differentiated from patients with OA, SLE, and HC. Three urinary lipids showing differential expression between RA from HC were identified with an accuracy of 84%, but they failed to differentiate RA from OA. There were five lipid pathways that differed between seronegative and seropositive RA. Conclusion: Here, we identified a panel of ten serum lipids as potential biomarkers that can differentiate RA from OA and SLE, regardless of seropositivity. In addition, three urinary lipids had diagnostic utility for differentiating RA from HC.

P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy After Deployment of a Drug-Eluting Stent: The SHARE Randomized Clinical Trial.

Importance: P2Y12 inhibitor monotherapy after dual antiplatelet therapy (DAPT; a P2Y12 inhibitor plus aspirin) for a brief duration has recently emerged as an attractive alternative for patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent. Objective: To investigate whether P2Y12 inhibitor monotherapy after 3 months of DAPT was noninferior to 12 months of DAPT following PCI with a drug-eluting stent. Design, Setting, and Participants: The Short-Term Dual Antiplatelet Therapy After Deployment of Bioabsorbable Polymer Everolimus-Eluting Stent (SHARE) open-label, noninferiority randomized clinical trial was conducted from December 15, 2017, through December 14, 2020. Final 1-year clinical follow-up was completed in January 2022. This study was a multicenter trial that was conducted at 20 hospitals in South Korea. Patients who underwent successful PCI with bioabsorbable polymer everolimus-eluting stents were enrolled. Interventions: Patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (n = 694) or 12 months of DAPT (n = 693). Main Outcomes and Measures: The primary outcome was a net adverse clinical event, a composite of major bleeding (based on Bleeding Academic Research Consortium type 3 or type 5 bleeding) and major adverse cardiac and cerebrovascular events (cardiac death, myocardial infarction, stent thrombosis, stroke, or ischemia-driven target lesion revascularization) between 3 and 12 months after the index PCI. The major secondary outcomes were major adverse cardiac and cerebrovascular events and major bleeding. The noninferiority margin was 3.0%. Results: Of the total 1452 eligible patients, 65 patients were excluded before the 3-month follow-up, and 1387 patients (mean [SD] age, 63.0 [10.7] years; 1055 men [76.1%]) were assigned to P2Y12 inhibitor monotherapy (n = 694) or DAPT (n = 693). Between 3 and 12 months of follow-up, the primary outcome (using Kaplan-Meier estimates) occurred in 9 patients (1.7%) in the P2Y12 inhibitor monotherapy group and in 16 patients (2.6%) in the DAPT group (absolute difference, -0.93 [1-sided 95% CI, -2.64 to 0.77] percentage points; P < .001 for noninferiority). For the major secondary outcomes (using Kaplan-Meier estimates), major adverse cardiac and cerebrovascular events occurred in 8 patients (1.5%) in the P2Y12 inhibitor monotherapy group and in 12 patients (2.0%) in the DAPT group (absolute difference, -0.49 [95% CI, -2.07 to 1.09] percentage points; P = .54). Major bleeding occurred in 1 patient (0.2%) in the P2Y12 inhibitor monotherapy group and in 5 patients (0.8%) in the DAPT group (absolute difference, -0.60 [95% CI, -1.33 to 0.12] percentage points; P = .10). Conclusions and Relevance: In patients with coronary artery disease undergoing PCI with the latest generation of drug-eluting stents, P2Y12 inhibitor monotherapy after 3-month DAPT was not inferior to 12-month DAPT for net adverse clinical events. Considering the study population and lower-than-expected event rates, further research is required in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT03447379.

In Vitro Anti-Inflammatory and Skin Protective Effects of Codium fragile Extract on Macrophages and Human Keratinocytes in Atopic Dermatitis.

Codium fragile has been traditionally used in oriental medicine to treat enterobiasis, dropsy, and dysuria, and it has been shown to possess many biological properties. Atopic dermatitis (AD) is one of the types of skin inflammation and barrier disruption, which leads to chronic inflammatory skin diseases. In the current investigation, the protective effects of C. fragile extract (CFE) on anti-inflammation and skin barrier improvement were investigated. In LPS-stimulated RAW 264.7 cells, nitric oxide generation and the expression levels of interleukin (IL)-1ß, IL-4, IL-6, iNOS, COX-2, and tumor necrosis factor-alpha (TNF)-α were reduced by CFE. CFE also inhibited the phosphorylation of NF-κB-p65, ERK, p-38, and JNK. Additionally, CFE showed inhibitory activity on TSLP and IL-4 expression in HaCaT cells stimulated with TNF-α/interferon-gamma (IFN-γ). Enhanced expression of factors related to skin barrier function, FLG, IVL, and LOR, was confirmed. These findings implied that CFE may be used as a therapeutic agent against AD due to its skin barrier-strengthening and anti-inflammatory activities, which are derived from natural marine products.

In vitro immune-enhancing effects of Platycodon grandiflorum combined with Salvia plebeian via MAPK and NF-κB signaling in RAW264.7 cells.

The immune-enhancing activity of the combination of Platycodon grandiflorum and Salvia plebeian extracts (PGSP) was evaluated through macrophage activation using RAW264.7 cells. PGSP (250-1000 µg/mL) showed a higher release of NO in a dose-dependent manner. The results showed that PGSP could significantly stimulate the production of PGE2, COX-2, TNF-α, IL-1ß, and IL-6 in RAW264.7 cells and promote iNOS, COX-2, TNF-α, IL-1ß, IL-4, and IL-6 mRNA expression. Western blot analysis demonstrated that the protein expression of iNOS and COX-2 and the phosphorylation of ERK, JNK, p38, and NF-κB p65 were greatly increased in PGSP-treated cells. PGSP also promoted the phagocytic activity of RAW264.7 cells. All these results indicated that PGSP might activate macrophages through MAPK and NF-κB signaling pathways. Taken together, PGSP may be considered to have immune-enhancing activity and might be used as a potential immune-enhancing agent.

Immune Enhancement Effects of Neutral Lipids, Glycolipids, Phospholipids from Halocynthia aurantium Tunic on RAW264.7 Macrophages.

Fractionated lipids of Halocynthia aurantium (Pyuridae) have been demonstrated to possess anti-inflammatory properties. However, their modulatory properties have not been reported yet. Thus, the objective of this study was to determine immune enhancing effects of fractionated lipids from H. aurantium tunic on macrophage cells. The tunic of H. aurantium was used to isolate total lipids, which were then subsequently separated into neutral lipids, glycolipids, and phospholipids. RAW264.7 cells were stimulated with different concentrations (0.5, 1.0, 2.0, and 4.0%) of each fractionated lipid. Cytotoxicity, production of NO, expression levels of immune-associated genes, and signaling pathways were then determined. Neutral lipids and glycolipids significantly stimulated NO and PGE2 production and expression levels of IL-1ß, IL-6, TNF-α, and COX-2 in a dose-dependent manner, while phospholipids ineffectively induced NO production and mRNA expression. Furthermore, it was found that both neutral lipids and glycolipids increased NF-κB p-65, p38, ERK1/2, and JNK phosphorylation, suggesting that these lipids might enhance immunity by activating NF-κB and MAPK signaling pathways. In addition, H. aurantium lipids-induced TNF-α expression was decreased by blocking MAPK or NF-κB signaling pathways. Phagocytic activity of RAW 264.7 cells was also significantly enhanced by neutral lipids and glycolipids. These results suggest that neutral lipids and glycolipids from H. aurantium tunic have potential as immune-enhancing materials.

Inhibitory effects of Oncorhynchus mykiss lipids in LPS-induced RAW264.7 cells via suppression of NF-κB and MAPK pathways.

Oncorhynchus mykiss, a significant aquaculture species, possesses compounds with numerous biological and pharmacological functions, including antioxidant, anticancer, anti-microbial, and anti-obesity effects. However, possible anti-inflammatory effects of lipids extracted from O. mykiss eggs on RAW264.7 cells induced by LPS have not been elucidated yet. The current study identified 13 fatty acids in lipids extracted from O. mykiss eggs that contained high amounts (51.92% of total fatty acids) of polyunsaturated fatty acids (PUFAs), especially DHA (33.66%) and EPA (7.77%). These O. mykiss lipids (100-400 µg/mL) showed significant anti-inflammatory effects by inhibiting NO and iNOS expression in LPS-stimulated RAW264.7 cells. They also inhibited expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α, while upregulating anti-inflammatory cytokines IL-10, IL-11, and TGF-ß. These lipids from O. mykiss effectively inhibited LPS-induced expression CD86 as a surface biomarker on RAW264.7 cells. Additionally, O. mykiss lipids suppressed phosphorylation of p38, JNK, and ERK1/2 and the expression of phosphorylated NF-κB subunit p65. These findings indicate that O. mykiss lipids possess anti-inflammatory properties by inhibiting NF-κB and MAPK signaling pathways.

Evaluation of immunogenicity-induced DNA vaccines against different SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic worldwide. As of September 2023, the number of confirmed coronavirus cases has reached over 770 million and caused nearly 7 million deaths. The World Health Organization assigned and informed the characterization of variants of concern (VOCs) to help control the COVID-19 pandemic through global monitoring of circulating viruses. Although many vaccines have been proposed, developing an effective vaccine against variants is still essential to reach the endemic stage of COVID-19. We designed five DNA vaccine candidates composed of the first isolated genotype and major SARS-CoV-2 strains from isolated Korean patients classified as VOCs, such as Alpha, Beta, Gamma, and Delta. To evaluate the immunogenicity of each genotype via homologous and heterologous vaccination, mice were immunized twice within a 3-week interval, and the blood and spleen were collected 1 week after the final vaccination to analyze the immune responses. The group vaccinated with DNA vaccine candidates based on the S genotype and the Alpha and Beta variants elicited both humoral and cellular immune responses, with higher total IgG levels and neutralizing antibody responses than the other groups. In particular, the vaccine candidate based on the Alpha variant induced a highly diverse cytokine response. Additionally, we found that the group subjected to homologous vaccination with the S genotype and heterologous vaccination with S/Alpha induced high total IgG levels and a neutralization antibody response. Homologous vaccination with the S genotype and heterologous vaccination with S/Alpha and S/Beta significantly induced IFN-γ immune responses. The immunogenicity after homologous vaccination with S and Alpha and heterologous vaccination with the S/Alpha candidate was better than that of the other groups, indicating the potential for developing novel DNA vaccines against different SARS-CoV-2 variants.

Inhibitory effects of polysaccharides from Korean ginseng berries on LPS-induced RAW264.7 macrophages.

Polysaccharides isolated from Korean ginseng berries (GBPs) have shown beneficial effects such as immunomodulatory, anti-inflammatory, anti-cancer, and anti-diabetic properties. However, little is known about anti-inflammatory effects of GBPs. Thus, the purpose of this study was to investigate anti-inflammatory properties of four fractions of GBPs, namely GBP-C, GBP-F1, GBP-F2, and GBP-F3, in macrophages. Their toxicities and effects on NO production in RAW264.7 cells were assessed by culturing cells with various concentrations of GBPs and stimulating cells with LPS. Furthermore, expression levels of inflammatory mediators, cytokines, cell surface molecules, and immune signaling pathways were evaluated in LPS-stimulated macrophages using different fractions of GBPs at 450 µg/mL. These GBPs activated LPS-stimulated RAW264.7 cells to significantly reduce NO production. They suppressed the expression of mRNA and cell surface molecules via MAPK and NF-κB pathways. Collectively, results revealed that all four GBP fractions showed anti-inflammatory effects, with GBP-F1 having a more efficient anti-inflammatory effect than GBP-C, GBP-F2, and GBP-F3. The structure of GBP-F1 mainly consists of 1 → 3)- Araf, 1 → 4)- Glcp, and 1 → 6)-Galp glycosidic linkages. These results demonstrate that GBPs can be employed as alternative natural sources of anti-inflammatory agents.

In Vitro Anti-Inflammatory Activity and Structural Characteristics of Polysaccharides Extracted from Lobonema smithii Jellyfish.

Crude polysaccharides were extracted from the white jellyfish (Lobonema smithii) using water extraction and fractionated using ion-exchange chromatography to obtain three different fractions (JF1, JF2, and JF3). The chemical characteristics of four polysaccharides were investigated, along with their anti-inflammatory effect in LPS-stimulated RAW264.7 cells. All samples mainly consisted of neutral sugars with minor contents of proteins and sulphates in various proportions. Glucose, galactose, and mannose were the main constituents of the monosaccharides. The molecular weights of the crude polysaccharides and the JF1, JF2, and JF3 fractions were 865.0, 477.6, 524.1, and 293.0 kDa, respectively. All polysaccharides were able to decrease NO production, especially JF3, which showed inhibitory activity. JF3 effectively suppressed iNOS, COX-2, IL-1ß, IL-6, and TNF-α expression, while IL-10 expression was induced. JF3 could inhibit phosphorylated ERK, JNK, p38, and NF-κB p65. Furthermore, flow cytometry showed the impact of JF3 on inhibiting CD11b and CD40 expression. These results suggest that JF3 could inhibit NF-κB and MAPK-related inflammatory pathways. The structural characterisation revealed that (1→3)-linked glucopyranosyl, (1→3,6)-linked galactopyranosyl, and (1→3,6)-linked glucopyranosyl residues comprised the main backbone of JF3. Therefore, L. smithii polysaccharides exhibit good anti-inflammatory activity and could thus be applied as an alternative therapeutic agent against inflammation.

Arctoscopus japonicus Lipids Enhance Immunity of Mice with Cyclophosphamide-Induced Immunosuppression.

A lipid extract was obtained from eggs of the sailfin sandfish, Arctoscopus japonicus. Immunostimulatory effects of A. japonicus lipids incorporated with PEG6000 (AJ-PEG) on immunosuppressed mice treated with cyclophosphamide (CY) were investigated. AJ-PEG was administered orally to mice at different concentrations of 25 to 100 mg/kg body weight (BW). CY was injected to mice intraperitoneally at 80 mg/kg BW. Administration of AJ-PEG significantly increased the spleen index of CY-treated mice. AJ-PEG also stimulated the proliferation of splenic lymphocytes and natural killer (NK) activity. Immune-associated cytokines such as IL-1ß, IL-2, IL-4, IL-6, TNF-α, and IFN-γ as well as TLR4 were overexpressed in splenic lymphocytes. Furthermore, AJ-PEG significantly increased splenic CD4+ and CD8+ T lymphocytes. In peritoneal macrophages, AJ-PEG administration improved proliferation, nitric oxide (NO) production, and phagocytosis. It also upregulated iNOS, COX-2, IL-1ß, IL-6, and TNF-α expression. Taken together, these results suggest that AJ-PEG can be used in animal models with immunosuppressive conditions as a potent immunomodulatory agent.

Probiotic Properties and Safety Evaluation of Lactobacillus plantarum HY7718 with Superior Storage Stability Isolated from Fermented Squid.

The aim of this study was to identify new potential probiotics with improved storage stability and to evaluate their efficacy and safety. Sixty lactic acid bacteria strains were isolated from Korean traditional fermented foods, and their survival was tested under extreme conditions. Lactobacillus plantarum HY7718 (HY7718) showed the greatest stability during storage. HY7718 also showed a stable growth curve under industrial conditions. Whole genome sequencing revealed that the HY7718 genome comprises 3.26 Mbp, with 44.5% G + C content, and 3056 annotated Protein-coding DNA sequences (CDSs). HY7718 adhered to intestinal epithelial cells and was tolerant to gastric fluids. Additionally, HY7718 exhibited no hemolytic activity and was not resistant to antibiotics, confirming that it has probiotic properties and is safe for consumption. Additionally, we evaluated its effects on intestinal health using TNF-induced Caco-2 cells. HY7718 restored the expression of tight junction proteins such as zonular occludens (ZO-1, ZO-2), occludin (OCLN), and claudins (CLDN1, CLDN4), and regulated the expression of myosin light-chain kinase (MLCK), Elk-1, and nuclear factor kappa B subunit 1 (NFKB1). Moreover, HY7718 reduced the secretion of proinflammatory cytokines such as interleukin-6 (IL-6) and IL-8, as well as reducing the levels of peroxide-induced reactive oxygen species. In conclusion, HY7718 has probiotic properties, is safe, is stable under extreme storage conditions, and exerts positive effects on intestinal cells. These results suggest that L. plantarum HY7718 is a potential probiotic for use as a functional supplement in the food industry.

A New Wave of Targeting 'Undruggable' Wnt Signaling for Cancer Therapy: Challenges and Opportunities.

Aberrant Wnt signaling activation is frequently observed in many cancers. The mutation acquisition of Wnt signaling leads to tumorigenesis, whereas the inhibition of Wnt signaling robustly suppresses tumor development in various in vivo models. Based on the excellent preclinical effect of targeting Wnt signaling, over the past 40 years, numerous Wnt-targeted therapies have been investigated for cancer treatment. However, Wnt signaling-targeting drugs are still not clinically available. A major obstacle to Wnt targeting is the concomitant side effects during treatment due to the pleiotropic role of Wnt signaling in development, tissue homeostasis, and stem cells. Additionally, the complexity of the Wnt signaling cascades across different cancer contexts hinders the development of optimized targeted therapies. Although the therapeutic targeting of Wnt signaling remains challenging, alternative strategies have been continuously developed alongside technological advances. In this review, we give an overview of current Wnt targeting strategies and discuss recent promising trials that have the potential to be clinically realized based on their mechanism of action. Furthermore, we highlight new waves of Wnt targeting that combine recently developed technologies such as PROTAC/molecular glue, antibody-drug conjugates (ADC), and anti-sense oligonucleotides (ASO), which may provide us with new opportunities to target 'undruggable' Wnt signaling.

Korean Ginseng Berry Polysaccharide Enhances Immunomodulation Activities of Peritoneal Macrophages in Mice with Cyclophosphamide-Induced Immunosuppression.

Korean ginseng (Panax ginseng C. A. Meyer), a member of the Araliaceae family, is known as a traditional medicinal plant to have a wide range of health properties. Polysaccharides constitute a major component of Korean ginseng, and its berries exhibit immune-modulating properties. The purpose of this study was to investigate the immune effects of crude polysaccharide (GBPC) extracted from Korean ginseng berry on peritoneal macrophages in mice with cyclophosphamide (CY)- induced immunosuppression. BALB/c mice were divided into eight groups: normal control, normal control + CY, levamisole + CY, ginseng + CY, and four concentrations of 50, 100, 250, and 500mg/kg BW/day of GBPC + CY. Mice were orally administered with samples for 10 days. Immunosuppression was established by treating mice with CY (80 mg/kg BW/day) through intraperitoneal injection on days 4 to 6. The immune function of peritoneal macrophages was then evaluated. Oral administration of 500mg/kg BW/day GBPC resulted in proliferation, NO production, and phagocytosis at 100%, 88%, and 91%, respectively, close to the levels of the normal group (100%) of peritoneal macrophages. In CY-treated mice, GBPC of 50-500 mg/kg BW/day also dose-dependently stimulated the proliferation, NO production, and phagocytosis at 56-100%, 47-88%, and 53-91%, respectively, with expression levels of immune-associated genes, such as iNOS, COX-2, IL-1ß, IL-6, and TNF-α, of about 0.32 to 2.87-fold, compared to those in the CY group. GBPC could be a potential immunomodulatory material to control peritoneal macrophages under an immunosuppressive condition.

In Vitro Immune-Enhancement and Anti-Inflammatory Effects of Fatty Acids Extracted from the Halocynthia aurantium Gonad on RAW264.7 Macrophages.

Fatty acids extracted from the Halocynthia aurantium gonad (HAGF) were shown to be primarily composed of the highest concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at 41% and 17% of total fatty acids, respectively. In the present study, HAGF were examined for their immunostimulant and anti-inflammatory effects on RAW264.7 macrophage cells. HAGF were found to significantly boost nitric oxide (NO) production and increase the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor (TNF)-α expression in a dose-dependent manner. Moreover, the phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK), extracellular signal-regulated kinase (ERK), p38, and nuclear factor κB (NF-κB) p65 was up-regulated by the stimulation of RAW264.7 cells with HAGF. When lipopolysaccharide (LPS)-stimulated the macrophages, they also exhibited anti-inflammatory activity via decreasing NO production and immune-related gene expression, Cluster of differentiation (CD) 86 expression, and protein levels in the NF-κB and mitogen-activated protein kinases (MAPK) signaling pathways. Overall, these results indicate that HAGF exert immune-modulatory effects in macrophages.

Development of fermented rice cake containing strawberry showing anti-inflammatory effect on LPS-stimulated macrophages and paw edema induced mice.

Strawberry (Fragaria ananassa) is one of the richest sources containing a wide variety of nutritive compounds. Anti-inflammatory activities of fermented rice cake made of strawberry powder as well as rice powder were evaluated. The fermented rice cake containing strawberry powder (SRC) significantly and dose-dependently inhibited NO production in LPS-stimulated RAW264.7 cells without cytotoxicity. Also, SRC effectively suppressed inflammatory gene expression, including iNOS, COX-2, IL-1ß, IL-6, and TNF-α. In addition, the production of PGE2, IL-1ß, IL-6, and TNF-α was significantly reduced. Furthermore, the anti-inflammatory effect of SRC was investigated using carrageenan-induced paw edema of ICR mice. It was demonstrated that pre-orally administration of SRC at a dose of 50 and 100 mg/kg BW significantly inhibited paw edema induced by carrageenan. This study suggested that the anti-inflammation activities of strawberry rice cake give the potential for increasing the commercialization of rice cake and rice products.

Anti-inflammatory properties of neutral lipids, glycolipids, and phospholipids isolated from Ammodytes personatus eggs in LPS-stimulated RAW264.7 cells.

In the present study, total lipids were extracted from Ammodytes personatus eggs and separated into neutral lipids, glycolipids, and phospholipids. The anti-inflammatory activity of the neutral lipids, glycolipids, and phospholipids was investigated in macrophages, as well as the fatty acid profiles of the lipids. Palmitic acid, oleic acid, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were the primary fatty acids in the three fractionated lipids. Among the lipids, the phospholipids contained the highest concentration of polyunsaturated fatty acids (PUFAs), particularly DHA and EPA (31.89 and 16.93% of the total fatty acids, respectively). The anti-inflammatory effects of the three lipids isolated from A. personatus eggs were analyzed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The three lipids significantly reduced nitric oxide (NO) production and the mRNA expression of immune-associated genes in a dose-dependent manner. All lipids down-regulated the protein expression of phosphorylated NF-κB-p65 and MAPK (p38, JNK, and ERK1/2) signaling pathways, suggesting that they could inhibit cell signaling pathways by activating NF-κB and MAPK. The expression of CD40 and CD86 in LPS-stimulated RAW264.7 cells was also significantly decreased by A. personatus lipids. Consequently, the neutral lipids, glycolipids, and phospholipids from A. personatus eggs could serve as anti-inflammatory agents.

Anti-inflammatory effects of neutral lipids, glycolipids, phospholipids from Halocynthia aurantium tunic by suppressing the activation of NF-κB and MAPKs in LPS-stimulated RAW264.7 macrophages.

Halocynthia aurantium is a marine organism that has been considered a promising source for bio-functional materials. Total lipids were extracted from H. aurantium tunic, and then they were separated into neutral lipids, glycolipids, and phospholipids. In the present study, fatty acid profiles of three lipids and their anti-inflammatory effects in RAW264.7 cells were investigated. Among the lipid classes, phospholipids showed the diversity of fatty acid constituents, compared with the glycolipids and neutral lipids. Three lipids contain different contents of fatty acids depending on the kinds of lipids. The most contents were saturated fatty acids (SFAs, 53-69% of the fatty acids) and monounsaturated fatty acids (MUFAs, 15-17% of fatty acids) and polyunsaturated fatty acids (PUFAs, 14-32% of fatty acids) are followed. H. aurantium lipids not only dose-dependently inhibited nitric oxide production but also reduced the expression of inflammatory cytokine genes such as TNF-α, IL-1ß, and IL-6 in LPS-stimulated macrophages. It was also demonstrated that the expression of COX-2 was dose-dependently suppressed. Moreover, H. aurantium lipids decreased phosphorylation of NF-κB p-65, p38, ERK1/2, and JNK, suggesting that three lipids from H. aurantium tunic provide anti-inflammatory effects through NF-κB and MAPK signaling. These results indicate that H. aurantium is a potential source for anti-inflammation.

Vascular Alterations Preceding Arterial Wall Thickening in Overweight and Obese Children.

BACKGROUND: Childhood obesity is linked to adverse cardiovascular outcomes in adulthood. This study aimed to assess the impact of childhood obesity on the vasculature and to investigate whether vascular alteration precedes arterial wall thickening in childhood. METHODS: A total of 295 overweight (body mass index [BMI] 85th to 95th percentile, n = 30) and obese (BMI ≥ 95th percentile, n = 234) children aged 7-17 years and 31 normal-weight controls with similar age and gender were prospectively recruited. We assessed anthropometric data and laboratory findings, and measured the carotid intima-media thickness (IMT), carotid artery (CA) diameter, M-mode-derived arterial stiffness indices, and velocity vector imaging parameters, including the CA area, fractional area change, circumferential strain, and circumferential strain rate (SR). RESULTS: The mean ± standard deviation age of the participants was 10.8 ± 2.1 years; 172 (58%) children were male. Regarding structural properties, there was no difference in the IMT between the three groups. The CA diameter was significantly increased in obese children, whereas the CA area showed a significant increase beginning in the overweight stage. Regarding functional properties, contrary to ß stiffness and Young's elastic modulus, which were not different between the three groups, the circumferential SR showed a significant decrease beginning in the overweight stage and was independently associated with BMI z-scores after adjusting for covariates. CONCLUSION: We have demonstrated that arterial stiffening and arterial enlargement precede arterial wall thickening, and that these vascular alterations begin at the overweight stage in middle childhood or early adolescence.